Overexpression of TMEM47 Induces Tamoxifen Resistance in Human Breast Cancer Cells

Men, Xin; Su, Mengyang; Jun, Ma; Mou, Yueyang; Dai, Peng; Chen, Chao; Cheng, Xi

doi:10.1177/15330338211004916

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…The binding of EGR1 to the NGFR promoter has been previously shown [18], suggesting that EGR1 might act in concert with ATF3 and tightly controls the expression of CD271 during phenotype switching. Finally, we investigated the potential regulation of general markers of melanoma (PD-L1, MET) and of additional mediators of stemness and phenotype switching in addition to NGFR, such as SOX9, ATF3 and TMEM47 [26][27][28][29][30][31][32] in RFP-positive (RFP) or RFP-negative (−) sorted cells four and eight days after sorting. We observed increased expression levels from day four to eight; ATF3 and NGFR, in particular, revealed a steady increase in expression levels (Figure S2C).…”

Section: Ngfr/rfp + Cells Are Enriched Upon Dabrafenib Treatment Refl...mentioning

confidence: 99%

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Vidal

Redmer

2022

IJMS

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Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity, which in turn determine tumor cell responses towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug-resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here, we establish a dual-reporter system, enabling the tracking of NGFR expression and mRNA stability and providing insights into the maintenance of NCSC states. We observed that a transcriptional reporter that contained a 1-kilobase fragment of the human NGFR promoter was activated only in a minor subset (0.72 ± 0.49%, range 0.3–1.5), and ~2–4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provides insights into phenotype switching and reveals that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene-set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor-treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provides insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

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Section: Ngfr/rfp + Cells Are Enriched Upon Dabrafenib Treatment Refl...mentioning

confidence: 99%

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Vidal

Redmer

2022

IJMS

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“…The binding of EGR1 to the NGFR promoter was previously shown 35 , suggesting that EGR1 might act in concert with ATF3 and tightly controlled the expression of CD271 during phenotype switching. Finally, we investigated the potential regulation of general markers of melanoma (PD-L1, MET) and of additional mediators of stemness and phenotype switching besides NGFR such as SOX9, ATF3 and TMEM47 [36][37][38][39][40][41][42] in RFP positive (RFP) or negative (-) sorted cells four and eight days after sorting. We observed increased expression levels from day four to eight, particular ATF3 and NGFR revealed a steady increase in expression levels (Figure S2C).…”

Section: Ngfr/rfp + Cells Are Enriched Upon Dabrafenib Treatment Refl...mentioning

confidence: 99%

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Vidal¹,

Redmer²

2022

Preprint

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Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was activated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provided insights into phenotype switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

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“…It has been confirmed that TMEM47 is located in the NC_000023.11 region and includes three exons. Studies have shown that the gene is expressed in the bladder, adipose and 23 other tissues and found that the overexpression of TMEM47 may induce resistance in patients to certain chemotherapy drugs [51,52]. The four point estimates ( γGBN , γGBU , γGPF and γGF ) of γ for the gene are 0.4703, 0.4547, 0.4816 and 0.4847, and the 95% HPDIs or CIs derived by the GBN, GBU, PF and Fieller's methods are (0.0023, 1.2380), (0.0337, 1.3083), (0.0562, 1.2410) and (0.0557, 1.3896), respectively.…”

Section: Application To Mctfr Datamentioning

confidence: 99%

Gene-Based Methods for Estimating the Degree of the Skewness of X Chromosome Inactivation

Yuan

Zhu

et al. 2022

Genes

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Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases, and currently several methods have been proposed to estimate the degree of the XCI-S (denoted as γ) for a single locus. However, no method has been available to estimate γ for genes. Therefore, in this paper, we first propose the point estimate and the penalized point estimate of γ for genes, and then derive its confidence intervals based on the Fieller’s and penalized Fieller’s methods, respectively. Further, we consider the constraint condition of γ∈[0, 2] and propose the Bayesian methods to obtain the point estimates and the credible intervals of γ, where a truncated normal prior and a uniform prior are respectively used (denoted as GBN and GBU). The simulation results show that the Bayesian methods can avoid the extreme point estimates (0 or 2), the empty sets, the noninformative intervals ([0, 2]) and the discontinuous intervals to occur. GBN performs best in both the point estimation and the interval estimation. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use. In summary, in practical applications, we recommend using GBN to estimate γ of genes.

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Overexpression of TMEM47 Induces Tamoxifen Resistance in Human Breast Cancer Cells

Cited by 4 publications

References 22 publications

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Tracking of Melanoma Cell Plasticity by Transcriptional Reporters

Gene-Based Methods for Estimating the Degree of the Skewness of X Chromosome Inactivation

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